This randomized clinical trial (RCT) continues the work of the National Acute Spinal Cord Injury Study (NASCIS) group in attempting to treat patients with acutely injured spinal cords by pharmacologic therapy. Previous animal work has suggested that some of the permanent disability from this injury results from biochemical and physical degradation of the spinal cord in the hours following injury. Several mechanisms are likely to be responsible for this "secondary injury" including decreased blood flow, metabolic dysfunction, protein degradation, and lipid peroxidation. The notion that early drug therapy may improve permanent neurologic recovery after acute spinal cord injury recently received support from the results of a prior RCT (NASCIS 2) conducted by us. The proposed RCT of 495 patients will compare the best treatment arm of NASCIS 2 (30 mg/kg bolus of methylprednisolone followed by a 23-hour infusion of 5.4 mg/kg) with the same dose of methylprednisolone extended for 48 hours. A third treatment arm will use the aminosteroid tirilazad at a dose of 1.5 mg/kg every six hours for 48 hours after an initial bolus of methylprednisolone (30 mg/kg). Tirilazad is a new class of aminosteroid which has proven to be efficacious in animal models of acute spinal cord injury. An escalating dose phase 2 study at three NASCIS centers has shown tirilazad to be free of toxicity at the planned study dose. Neurological function is assessed in the emergency room and 72 hours, 6 weeks, 6 months and one year post injury. Functional status is evaluated during the last three follow-up exams. NASCIS has over twelve years of experience in conducting RCTs in acute spinal cord injury. While this injury is now known to be amenable to treatment, recovery of lost function is modest, and further significant improvements in recovery from the catastrophic injury need to be empirically documented in properly controlled studies.